RESEARCH ARTICLE
C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics Vasilios Devetzis1, Arezoo Daryadel2, Stefanos Roumeliotis3, Marios Theodoridis3, Carsten A. Wagner2, Stefan Hettwer4, Uyen Huynh-Do1, Passadakis Ploumis3, Spyridon Arampatzis1* 1 Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital, Bern, Switzerland, 2 Institute of Physiology, University of Zurich, Zurich, Switzerland, 3 Department of Nephrology, University Hospital of Alexandroupoli, Alexandroupoli, Greece, 4 Neurotune AG, Schlieren, Switzerland *
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Abstract OPEN ACCESS Citation: Devetzis V, Daryadel A, Roumeliotis S, Theodoridis M, Wagner CA, Hettwer S, et al. (2015) C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics. PLoS ONE 10(12): e0143524. doi:10.1371/ journal.pone.0143524 Editor: Aristidis S. Charonis, Biomedical Research Foundation of the Academy of Athens, GREECE Received: September 24, 2015 Accepted: November 5, 2015 Published: December 2, 2015 Copyright: © 2015 Devetzis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was funded by a research Grant from the Commission for Technology and Innovation. Award Nr. CTI 15622.1. The funder provided support in the form of salaries for authors [VD], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this authors are articulated in the ‘author contributions’ section.
Background Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics.
Methods Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune1). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up. The presence of end stage renal disease (ESRD) was evaluated after 24 months followup. Correlation and logistic regression analyses were carried out to explore the associations of serum CAF levels with GFR, proteinuria, GFR loss and incident ESRD. Renal handling of CAF was tested in neurotrypsin-deficient mice injected with recombinant CAF.
Results We found a strong association of serum CAF levels with eGFR and a direct association with proteinuria both at baseline (r = 0.698, p
